Superoxides, scavenging

Bissett DL, Chatterjee R, Hannon DP (1990) Photoprotective effect of superoxide-scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse. Photodermatol Photoimmunol Photomed 7 56-62... 

Tsuji, A., Oka, S., Sano, Y., Matsushita, R., Takada, J., Sakurai, H., Superoxide scavenging activity and metal contents of coffee, Biomed. Res. Trace Elem., 6(2), 101, 1995. (CA124 230604h)... 

It is extremely important that the interaction of quinones with XO (Reaction (3)) is reversible that can lead to receiving erroneous results at the measurement of superoxide production by SOD-inhibitable cytochrome c reduction [28,29] (see also Chapter 27). Lusthof et al. [30] demonstrated that 2,5-bis(l-aziridinyl)-l,4-benzoquinones are directly reduced by XO. Interestingly at quinone concentrations greater than 25pmol I 1, quinones entirely suppressed one-electron reduction of dioxygen, and cytochrome c was completely reduced by the semiquinones formed. It is well known that cytochrome c and lucigenin are effective superoxide scavengers and due to that, these compounds are widely used in the quantitative assays of superoxide detection. Nonetheless, under certain experimental conditions they can be directly reduced by XO [31]. 

Many transition metal complexes have been considered as synzymes for superoxide anion dismutation and activity as SOD mimics. The stability and toxicity of any metal complex intended for pharmaceutical application is of paramount concern, and the complex must also be determined to be truly catalytic for superoxide ion dismutation. Because the catalytic activity of SOD1, for instance, is essentially diffusion-controlled with rates of 2 x 1 () M 1 s 1, fast analytic techniques must be used to directly measure the decay of superoxide anion in testing complexes as SOD mimics. One needs to distinguish between the uncatalyzed stoichiometric decay of the superoxide anion (second-order kinetic behavior) and true catalytic SOD dismutation (first-order behavior with [O ] [synzyme] and many turnovers of SOD mimic catalytic behavior). Indirect detection methods such as those in which a steady-state concentration of superoxide anion is generated from a xanthine/xanthine oxidase system will not measure catalytic synzyme behavior but instead will evaluate the potential SOD mimic as a stoichiometric superoxide scavenger. Two methodologies, stopped-flow kinetic analysis and pulse radiolysis, are fast methods that will measure SOD mimic catalytic behavior. These methods are briefly described in reference 11 and in Section 3.7.2 of Chapter 3. 

Fig. 10.10 c60 is a very effective scavenger of superoxide species. The standard superoxide scavenger, superoxide dismutase, is not nearly as effective (See Color Plates)... 

Superoxide dismutase Superoxide scavenging Yeast, mammals Fielden and Rotilio (1984)... 

Cos, P. et al., Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers, J. Nat. Prod., 61, 71, 1998. 

We have used the nitration of a tyrosine analog with superoxide dismutase to measure the peroxynitrite production from activated rat alveolar macrophages (Fig. 38). The estimated rate of peroxynitrite synthesis was estimated to be 0.1 nmol/10 cells/min (Ischiropoulos et al., 1992a). The rate of nitration was the same whether native Cu,Zn-superoxide dismutase or the phenylglyoxyl-H202 modified superoxide dismutase (which is >99% inhibited with respect to its superoxide scavenging activity) was used (Fig. 39). Three other independent but indirect estimates of peroxynitrite formation were consistent with the superoxide... 

J. P. Hu and co-workers, Structure-Activity Relationship ofFlavonoids with Superoxide Scavenging Activity, Biological Trace Element Research, Vol. 47, The Humana Press Inc., Clifton, N.J., pp. 327—331,1995. 

Jin F, Leitich J, von Sonntag C (1993) The superoxide radical reacts with tyrosine-derived phenoxyl radicals by addition rather than by electron transfer. J Chem Soc Perkin Trans 2 1583-1588 Jones CM, Lawrence A, Wardman P, Burkitt MJ (2002) Electron paramagnetic resonance with spin trapping investigation into the kinetics of glutathione oxidation by the superoxide radical re-evaluation of the rate constant. Free Rad Biol Med 32 982-900 Jones CM, Lawrence A, Wardman P, Burkitt MJ (2003) Kinetics of superoxide scavenging by glutathione an evaluation of its role in the removal of mitochondrial superoxide. Biochem Soc Trans 31 1337-1339... 

The production of superoxide anions is one of the major factors involved in NO toxicity because superoxide anions can react with NO to form the highly toxic free-radical peroxynitrite. A pivotal role for superoxide anions in NO-related insults is emphasized by results showing that transgenic mice overexpressing superoxide dismutase (SOD) are resistant to brain ischemia. Superoxide can protect against SNP-induced toxicity. Thus, the superoxide-scavenging properties of EGb 761 are likely to explain, at least in part, its ability to block cell death and the increase in reactive oxygen species accumulation induced by the two NO donors used here, SNP and SIN-1. 

This mechanism is consistent with a number of observations. Kinetic studies on prolyl 4-hydroxylase [223] and thymine hydroxylase (EC 1.14.11.6) [224] suggest that cofactor binds first, followed by 02. The bound 02 appears to have superoxide character, as superoxide scavengers are competitive inhibitors of 02 consumption [225,226], It is also clear that the oxidative decarboxylation of the keto acid is a distinct phase of the mechanism from the alkane functionalization step, as these two phases can be uncoupled, particularly when poor substrate analogs are employed [227-229], Evidence for an Fe(IV) = 0 intermediate derives from studies with substrate analogs. Besides the hydroxylation of the 5-methyl group of thymine, thymine hydroxylase can also catalyze ally lie hydrox-ylations, epoxidation of olefins, oxidation of sulfides to sulfoxides, and N-de-... 

---